1. Field of the Invention
The present invention relates to the problem of measuring the deformation of cantilevers, and in particular micro-cantilevers.
2. Description of the Related Art
The accurate measurement of cantilever deformation is a key issue in a number of different applications. For example, the atomic force microscope has for some time used deflection of a cantilever at the tip to measure the force between tip and sample.
More recently, arrays of cantilevers have been used as biosensors. It has been shown that when biochemically specific interactions occur between a ligand immobilized on one side of a cantilever and a receptor in solution, the cantilever bends due to a change in surface stress, which can be detected optically.
More generally, sensor arrays are very promising for application in disease diagnosis, drug screening, sensitive detection of very small concentrations of different substances, NOSE applications, fluid/gas flow, pressure sensors, and for temperature measurements. A nanomechanical actuation mechanism may be used, according to which cantilevers are microfabricated by standard low-cost silicon technology and, by virtue of the size achievable, are extremely sensitive to the presence of small molecule chemical and biological interactions, e.g. detecting femtomoles of biomolecules of DNA, and many other chemicals, including explosives.
The ability to detect multiple biomolecules has been limited to the number of fixed-end cantilevers that can be microfabricated. In addition, everyday clinical use has been challenging because the physical measurement apparatus could not be separated from the biochemical environment. Also, as in all fixed array-based combinatorial methods where scale-up is derived from increasing the number and density of elements in the array, chemical cross-contamination and physical cross-talk represent significant hurdles. These issues are discussed in E. D. Isaacs, M. Marcus, G. Aeppli, X. D. Xiang, X. D. Sun, P. Schultz, H. K. Kao, G. S. Cargill, and R. Haushalter, “Synchrotron x-ray microbeam diagnostics of combinatorial synthesis”, Applied Physics Letters 73(13), 1820 (1998).
FIG. 1 illustrates a typical prior art optical detection method, which relies on shining a fixed laser onto the free end of a tethered cantilever. However, such methods provide no information about the profile of bending and have limited scalability for microarray technology.
A number of different methods have been published describing how to measure the profile of cantilevers.
Tada et al. (H. Tada, A. E. Kumpel, R. E. Lathrop, J. B. Slanina, P. Nieva, P. Zavracky, I. N. Miaoulis, and P. Y. Wong, “Novel imaging system for measuring microscale curvatures at high temperatures”, Review of Scientific Instruments 71(1), 161 (2000)) disclose a method in which the deflection of a 100 μm cantilever is detected with a resolution of 1.5 μm. Since deflections for cantilever biosensors are expected to be below 200 nm (based on a 500 micron long, 100 micron wide, 1 micron thick silicon cantilever with a spring constant of 0.02 N/m, which corresponds to a surface stress change of approximately 30 mN/m), the technique of Tada et al is not suitable for such applications.
S. Jeon and T. Thundat, “Instant curvature measurement for microcantilever sensors”, Applied Physics Letters 85(6), 1083 (2004) discloses an approach using a multiple-point deflection technique, where eight light-emitting diodes are focused on various positions of a cantilever. The main drawbacks for this method are the difficulty of aligning the eight lasers as well as evaluating large number of cantilevers.
J. Mertens, M. Alvarez, and J. Tamayo, “Real-time profile of microcantilevers for sensing applications”, Applied Physics Letters 87(23) (2005) discloses a technique in which the bending profile is acquired by optically rastering the cantilever. Drawbacks for this method are, first, the error introduced mechanically through the raster process and second, even more significant, the movement of the cantilever itself during the measurement.
Two methods have been published using optical interference.
Firstly, in the method disclosed in G. G. Yaralioglu, A. Atalar, S. R. Manalis, and C. F. Quate, “Analysis and design of an interdigital cantilever as a displacement sensor”, Journal of Applied Physics 83(12), 7405 (1998), interdigitated cantilevers are used, which allow for detecting the deflection of the free end of the cantilever only.
Secondly, in the method disclosed in M. Helm, J. J. Servant, F. Saurenbach, and R. Berger, “Read-out of micromechanical cantilever sensors by phase shifting interferometry”, Applied Physics Letters 87(6) (2005), the bending profile of the whole cantilever can be determined. However, the disclosed method relies on: a) the use of a point of reference on the cantilever support; and b) the interference of two beams, a reference beam and the reflected beam from the cantilever. The arrangement is complex and only applicable to tethered cantilevers.